Normal Reproductive function in male mice lacking pituitary kisspeptin receptor.

The anterior pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate gonadal development, gametogenesis and the secretion of the gonadal steroid hormones. The gonadotroph is primarily regulated by hypothalamic secretion of gonadotropin-releasing hormone (GnRH) from neurons of the rostral hypothalamus and is mediated by GnRH receptor signaling. Kisspeptin (KISS1)/kisspeptin receptor (KISS1R) signaling in GnRH neurons plays an essential role in reproductive function. As the kisspeptin receptor is present in the pituitary, kisspeptin signaling via the Kiss1r may regulate reproductive function at the level of pituitary. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO male and females have normal genital development, puberty onset, and fertility. Females have normal LH, FSH and estradiol while males had significantly increased basal serum FSH levels with no differences in basal serum LH, or testosterone levels. Overall, these findings indicate that the pituitary KISS1R does not play a role in male reproduction.

Recovery of Male Reproductive Function After Ceasing Prolonged Testosterone Undecanoate Injections

Context: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective: To investigate rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Methods: Men (n=303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo(P)-controlled randomized clinical trial of TU treatment were recruited for a further 12 months while remaining blinded to treatment. Sex steroids (T, DHT, E2, E1) by LCMS, LH, FSH and SHBG by immunoassays and sexual function questionnaires (Psychosexual Diary Questionnaire (PDQ), International Index of Erectile Function (IIEF), SF-12) were measured at entry (three months after last injection) and 6, 12, 18, 24, 40 and 52 weeks later. Results: In the nested cohort of TU-treated men, serum T was initially higher but declined to 12 weeks remaining stable thereafter with serum T and SHBG 11% and 13%, respectively, lower than P-treated men. Similarly, both questionnaires showed initial carryover higher scores in T-treated men, but after weeks 18 showed no difference between T and P treated men. Initially fully suppressed serum LH and FSH recovered slowly towards the participant’s own pre-treatment baseline over 12 months since last injection. Conclusions: After stopping 2 years of 1000 mg injectable TU treatment, full reproductive hormone recovery is slow and progressive over 15 months since last testosterone injection but may take longer than 12 months to be complete. Persistent proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than androgen deficiency.

The role of kisspeptin and MKRN3 in the diagnosis of central precocious puberty in girls

Objective: To evaluate the characteristics and significance of serum kisspeptin and MKRN3 levels for the diagnostic of central precocious puberty (CPP) in girls. Method: 34 individuals with CPP, 17 individuals with premature thelarche (PT) and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included of body mass index and tests for breast, bone and sexual characteristics were carried out. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3 and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90 and 120min after injection with triptorelin. Results: Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P=0.020), while serum MKRN3 levels lower in the two groups (P=0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P<0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40nmol/L, with 82.4% sensitivity and 57.1% specificity; while the cut-off value of serum MKRN3 was 0.33pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5. Conclusions: Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.

Evaluation of reproductive profile in male albino rats following varied duration of administration with Revive capsule

Background: Revive capsule is a polyherbal formulation commonly used to treat erectile dysfunction or enhance libido in men. Some of the individual herbs used in the formulation of this drug have been known scientifically to affect various biochemical components of the human body; hence this study was aimed at evaluating the reproductive profile in male albino rats following varied duration of administration with Revive capsule. Methods: A total of 42 male albino rats were used for the study, and were divided into six (6) groups of seven (7) rats each. They were allowed to acclimatize for two (2) weeks by maintaining 12-hour light and dark cycles daily, with access to standard feed and water ad libitum. Group A (negative control) rats were administered with distilled water once daily, while groups B, C, D, E and F were administered once daily with 72 mg/kg of Revive capsule for 1 week, 2 weeks, 3 weeks, 4 weeks and 6 weeks respectively. The rat dose administered was extrapolated from the human dose using the formula by Paget and Barnes. At the end of each treatment week, the rats were allowed to fast overnight, followed by their anaesthetization using chloroform, and blood sample collection via jugular vein puncture. Also, the testes were excised; the epididymis were also excised from the testes and used immediately for semen analysis, while the epididymis-free testes were examined histologically. Rat-specific test kits with ELISA method were used to analyze serum LH, FSH and testosterone.Results: The results showed a significant increase (p<0.05) in serum LH, FSH and testosterone levels, and a significant increase in sperm count and sperm quality parameters in the treatment groups compared to the negative control, with the maximum levels attained after 6 weeks of treatment (group F). Also, photomicrographs of histologically examined testes of the treatment groups appeared indifferent from those of the negative control.Conclusions: These findings may suggest that in using a rat model, treatment with Revive capsule at the appropriate dosage for 6 weeks is safe, and that, besides its acclaimed use in enhancing libido or treating erectile dysfunction, it may also be effective in promoting male fertility.

Serum gonadotropins, cortisol, PSA, and micronutrient levels among men with prostate carcinoma

Background Prostate cancer (PrCa) is a malignant tumour of the prostate that has many associated risk factors. There is continuous rise in the incidence among adult blacks which is a reflection of racial differences in testosterone concentrations. Methods The study involves 50 PrCa patients attending or referred to two tertiary health Institutions and 25 healthy men as controls. Weight and height of participants were measured, and body mass index (BMI) was calculated. Ten millilitres of venous blood sample was collected from each participant, allowed to clot, and then centrifuged at 5000 rpm for 5 min at room temperature (22–28 °C) to obtain the serum. Serum cortisol, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total prostate-specific antigen (TPSA), free prostate-specific antigen (FPSA), selenium, copper, magnesium, and zinc were determined. Prostate ultrasonography and biopsy were also done for histopathological studies. Result From this study, a significant increase (p < 0.05) in weight, BMI, serum FPSA, TPSA, and copper; a non-significant increase (p > 0.05) in serum cortisol, testosterone; a significant decrease (p < 0.05) in serum LH, selenium, zinc, and magnesium; and a non-significant decrease (p > 0.05) in serum FSH were observed among people living with PrCa when compared to the controls. However, no significant difference (p > 0.05) was observed in the height between the two groups. Ultrasonography and histology revealed evidence of prostatitis, hypertrophy, and carcinoma among the test group. Conclusion It can be concluded that PrCa is associated with increase serum cortisol, testosterone, and copper; and decreased serum LH, FSH, selenium, zinc, and magnesium concentrations and combination of biochemical, ultrasonographic, and histologic features are of diagnostic importance.

Optimal injection interval for testosterone undecanoate treatment of hypogonadal and transgender men

Objective: To define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice. Design and Methods: Prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for pathological hypogonadism or masculinization of female-to-male transgender (transmen) subject to individual dosing titration to achieve a stable replacement regimen. Results: From 2006 to 2019, 6899 injections were given to 325 consecutive patients. After excluding the 6-week loading dose, 6300 injections were given to 297 patients who had at least three and a median of 14 injections. The optimal injection interval (mean of last three injection intervals), had a median of 12.0 weeks (interquartile range 10.4–12.7 weeks). The interval was significantly influenced by age and body size (body surface area, BSA) but not by diagnosis or trough serum LH, FSH and SHBG. Longer (≥14 weeks; 68/297, 23%), but not shorter (≤10 weeks; 22/297, 7.4%), intervals were weakly correlated with age but not diagnosis or other covariables. Low blood hemoglobin increased with trough serum testosterone to reach plateau once testosterone was about 10 nmol/L or higher. Conclusion: Optimal intervals between TU injection after individual titration resulted in the approved 12-week interval in 70% of patients with only minor influence for clinical application of age and body size (BSA) and not of trough serum LH, FSH and SHBG. Individually optimised inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.

A study of the prevalence of gonadal dysfunction and its association with increasing disease severity in patients diagnosed with chronic kidney disease at a tertiary care center in Kolkata, West Bengal

Background: Hypergonadotropic hypogonadism is a well described hormonal derangement associated with chronic kidney disease, also known as uremic hypogonadism. The objective of this study was to assess the prevalence of gonadal dysfunction associated with chronic kidney disease and to study the co-relation of gonadal dysfunction with disease severity.Methods: In this cross-sectional observational study, 50 patients with diagnosed chronic kidney disease were included during the one-year period from May 2015 to April 2016. The clinical and biochemical parameters related to gonadal dysfunction were evaluated in these cases.Results: Out of the 28 male CKD patients, 19 (68%) patients had Serum Testosterone values less than 90 ng/dl, 18 (64%) patients had a serum leutinizing hormone (LH) level greater than 9 mIU/ml and 19 (68%) patients had a serum follicle stimulating hormone (FSH) level greater than 13 mIU/ml. Out of 22 female CKD patients, 14 (64%) patients had serum estradiol value less than 50 pg/ml, 12 (54%) patients had Serum LH level greater than 80 mIU/ml and 20 (91%) patients had a S. FSH level greater than 26 mIU/ml. Out of a total of 50 patients in this study, 34 patients showed evidence of gonadal dysfunction, the majority of them belonging to stage 5 CKD.Conclusions: Out of the 34 patients showing gonadal dysfunction, 5 (15%) patients were in stage 3 CKD, 11 (32%) patient were in stage 4 CKD and 18 (53%) were in stage 5 CKD. It may be proposed that gonadal dysfunction is very common in CKD patients and the frequency of sexual dysfunction increases as the renal function deteriorates.

Relationship Between 24-Hour Serum LH and Testosterone Concentrations and Their Interrelationships With Other Pituitary Hormones in Healthy Older Men

Background: With ageing, LH levels rise while T levels decline in men, although this decline in T levels could also be caused by a change in health status, including body composition, inflammation, and comorbidities. Not only levels of LH and T change with age, but levels of other pituitary hormones also change concomitantly with age. It could be hypothesized that these hormonal changes are synchronized with each other. Objective: In this study, we aimed to determine the relationship between 24-h serum LH and T concentrations in healthy older men. Besides, we aimed to determine which health factors, including body composition, metabolic and inflammatory markers, and LH-T related markers are associated with the strength of this LH-T relationship. Furthermore, we explored the interrelationships between LH and T with 24-h serum concentrations of GH, TSH, cortisol, and ACTH. Design: Hormones were measured in serum samples collected every 10 min during 24 h from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between two 24-h hormone concentration series for all possible time shifts. Results: A mean (95% confidence interval) maximal correlation coefficient of 0.21 (0.10 – 0.31) at lag time 60 min was found between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared to men with no LH-T relationship, lower fat mass (18.5 (14.9 – 19.7) vs. 22.3 (18.4 – 29.4) kg), waist circumference (93.6 (5.7) vs. 103.1 (12.0) cm), hsCRP levels (0.7 (0.4 – 1.3) vs. 1.8 (0.8 – 12.3) mg/L), IL-6 levels (0.8 (0.6 – 1.0) vs. 1.2 (0.9 – 3.0) pg/mL), and 24-h mean LH levels (4.3 (2.0) vs. 6.1 (1.5) U/L), and stronger LH-T feedforward synchrony (1.5 (0.3) vs. 1.9 (0.2)). Furthermore, T was positively cross-correlated with TSH (0.32 (0.21 – 0.43)), cortisol (0.26 (0.19 – 0.33)), and ACTH concentrations (0.26 (0.19 – 0.32)). Conclusions: LH concentrations were followed by T concentrations/secretion with a delay of 60 min in healthy older men, which is in line with literature. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, 24-h mean LH levels, and LH-T feedforward synchrony. In contrast, chronological age and 24-h mean T levels were not associated with the strength of the LH-T relationship. This observation could indicate that LH and health markers play a bigger role in determining the strength of LH-T cross-correlations than T and chronological age. Furthermore, we observed positive correlations between T and TSH, cortisol, and ACTH concentrations. These exploratory analyses could indicate that T and other hormones are driven by a common regulator or that there is crosstalk between these hormones.

MO865SEX HORMONAL PROFILE OF PATIENTS ON MAINTENANCE HEMODIALYSIS AND CORRELATION WITH QUALITY OF LIFE AND DEPRESSION: A CROSS-SECTIONAL STUDY FROM SOUTH INDIA

Background and Aims Hormonal abnormalities in haemodialysis (HD) patients contribute to quality of life including sexual dysfunction. Whereas Short Form 36 (SF 36) questionnaire deals with the holistic assessment of the quality of life in patients, it is directly impacted by sexual dysfunction or erectile dysfunction in males. In this study we assessed the sex hormone levels in HD patients and its correlation with quality of life (QOL). Method In this single center cross-sectional study, 100 patients (50 males and 50 females) on maintenance HD for more than 6 months were included in the study. In female patients’ sex hormones that included Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin, Estrogen, Progesterone was assessed in midweek early morning blood sample. In male patients LH, FSH and Testosterone were assessed in midweek early morning samples. QOL assessment was done using SF 36 questionnaire. Results Mean age of our study populations was 33.76+/- 7.86 years with male female ratio of 1:1 and mean body mass index of 20.52 ± 2.89 kg/m2. Presumed chronic interstitial nephritis in was the most common cause of end-stage renal disease (76%) in our study followed by Diabetic Kidney disease (21%). In males, mean serum LH, FSH and Testosterone were 8.58 ± 3.56 mIU/ml, 8.9 ± 4.05, 217.46 ± 96.44 ng/dl respectively with 70% patients having testosterone deficiency. In females, mean serum LH, FSH, Prolactin, estrogen and Progesterone levels were 8.61± 3.86 mIU/ml, 8.08 ± 3.70 mIU/ml, 12.35 ± 5.70 ng/ml, 84.56 ± 27.39 pg/ml and 0.31 ± 0.22ng/ml respectively. Mean SF 36 score in our study was 55.37+/-12.22, in males 54.82+/-12.81 and in females 55.93+/-11.70. The prevalence depression was 53% (50% in males and 56% in females) in our study. There was no significant correlation between SF 36 scores and Beck depression inventory (BDI) scores with LH, FSH in both the genders. In males there was positive correlation between SF 36 scores and testosterone level (r= 0.366), and in females positive correlation between SF 36 score and progesterone level in women HD patients (r= 0.549) was seen. There was a negative correlation between BDI score and progesterone level in women (r=0. -510) and negative correlation between BDI score and testosterone in men (r= -0.371). Conclusion QOL as assessed by SF 36 in patients on HD is low. There was positive correlation between SF 36 scores and testosterone level in males and between SF 36 score and progesterone in females.